Probing Guanidino Pendant or Bridged Groups in Cyclic Antimicrobial Peptides Derived from Temporin L: A Strategy to Improve Efficacy against Gram-Negative Bacteria.

ABSTRACT: The rise of antibiotic resistance underscores the urgent need for new antimicrobial agents. Antimicrobial peptides (AMPs), such as temporins, offer broad-spectrum activity through unique mechanisms but are often limited by cytotoxicity and poor stability. To improve the Gram-negative activity-to-toxicity ratio, we designed a focused library of cyclic Temporin L (TL) analogues bearing an additional positively charged guanidino group, introduced either as a side-chain pendant or as a bridged functionality. While guanidino modifications have been studied in side-chain peptide contexts, this represents the first application of guanidino-based bridging in AMP design. Among the synthesized compounds, four (e.g., 2, 6, 7 and 12) were selected based on the

SUBMITTER: Bellavita R 

PROVIDER: S-EPMC12703733 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature